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Yellow fever: Global threat

Yellow fever: Global threat. Jack Woodall, PhD Institute of Medical Biochemistry Federal University of Rio de Janeiro, Brazil (retired) (Formerly CDC & WHO Geneva). Not me!. ASTMH Annual Meeting, 16 Nov.2013. YF endemic zones. Background.

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Yellow fever: Global threat

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  1. Yellow fever:Global threat Jack Woodall, PhD Institute of Medical Biochemistry Federal University of Rio de Janeiro, Brazil (retired) (Formerly CDC & WHO Geneva) Not me! ASTMH Annual Meeting, 16 Nov.2013

  2. YF endemic zones

  3. Background • “Fears have long been held that if yellow fever were introduced to Asia it might spread widely and rapidly with • catastrophic human mortality and • subsequent establishment of a forest reservoir in primates or other animals • because of the presence of large populations of potential vector mosquitos (Aedesaegypti, A. albopictus).”

  4. Background (2) • “In 1954 a meeting of experts on yellow fever at Kuala Lumpur discussed the hazard of introduction of yellow fever to south and south-east Asia. “Trials of yellow fever vaccination in Malayan volunteers were subsequently carried out with the assistance of United Kingdom Colonial Development and Welfare.” (Gordon-Smith CE, Turner LH, Armitage P. 1962)

  5. Last Yellow fever epidemicsUSASailing-ship era • 1905 New Orleans, Louisiana, 8,399 cases) & Pensacola, Florida • 1911 last indigenous case http://www.gideononline.com

  6. Last Yellow fever epidemicsEUROPESailing-ship era 1861 France (St Nazaire) 44 cases, 24 deaths 1828 Gibraltar (UK) 1500 deaths

  7. Yellowfever, imported cases, 1999-present Airline era Netherlands 2000 Surinam

  8. What has changed in the last 10 years? • Yellowfeverin emergingphase

  9. Yellow fever in emerging phase 2013 AFRICA • WHO warningabouturbanization in West Africa2005 • Sudan & 5 more Africanoutbreaks 2012-13: oneongoingTODAY

  10. WEST AFRICA URBANIZATIONWHO ALERT • Date: 2005 • Source: WHO Global Alert and Response (GAR) • http://www.who.int/csr/disease/yellowfev/urbanoutbreaks/en/ • Increased risk of urban yellow fever outbreaks • The risk of large and uncontrollable outbreaks in urban areas in Africa is more likely than ever. • Accelerated urbanization has concentrated a non-immune population in settings where, high vector and population density, the main factors contributing to increased virus transmission are present.

  11. YELLOW FEVER – SUDAN(KORDOFAN) • Date: 14 Nov 2013 • Source: Radio Dabanga (Hilversum) • http://allafrica.com/stories/201311151118.html • According to the Sudanese Ministry of Health, between 3 Oct and 5 Nov [2013], a total of 22 suspected yellow fever cases, resulting in 7 deaths, occurred in West & South Kordofan, CFR 36.3%, OCHA reports in its latest Humanitarian Bulletin. 45 000 people to be vaccinated. -- Communicated by : ProMED-mail <promed@promedmail.org>

  12. Yellow fever in emerging phase 2013 SOUTH AMERICA Peru 2013 Bolivia2013 Brazil2012 (monkeydeaths) Source: ProMED <http://www.promedmail.org/>

  13. Yellow fever – Brazil: CDC Alert • Yellow Fever in Brazil -- OutbreakAlert2013 Because an outbreak of yellow fever was found in areas of Brazil outside of the reported yellow fever risk areas… Travelers should follow “enhanced precautions” for that risk area [Rio Grande do Sul & SW Sao Paulo states] by receiving the yellow fever vaccine. • Source: CDC <http://wwwnc.cdc.gov/travel/notices#travel-notice-definitions>

  14. Yellow fever in South Americaincreasing since 2008 ARGENTINA • 2008: Ministry of Health confirmed 5 cases of jungle yellow fever in Misiones Province • Source: ProMED http://promedmail.org/direct.php?id=20080401.1206 • The last outbreak of jungle yellow fever reported was in Corrientes in 1966 -- 47 years ago • Source: PAHO report <http://promedmail.org/direct.php?id=171703> Brazil Paraguay Misiones Corrientes Uruguay

  15. Yellow fever in South America increasing since 2008 BRAZIL • Outbreaks of YF -- typically occurring in Brazil every 7 years -- have become more frequent • YF has progressed to areas previously considered free • in Rio Grande do Sul(free since 1966) • & SW Sao Paulo state • These 2 areas previously posed no risk for YF, but between November 2008 and April 2009 they recorded 43 infections, with 16 deaths. • Source: O Estado de Sao Paulo, 21 May 2009 [in Portuguese] via ProMED <http://promedmail.org/direct.php?id=204930> [in English]

  16. What has changed in the last 10 years? • Yellowfeverin emergingphase • Dengue continues its worldwide spread

  17. * Map 2. Madeira (PT) 2005 *range of Aedes aegypti

  18. Dengue, Madeira (PT) 2012-13 • The island of Madeira, Portugal, experienced an outbreak of dengue, which began in October 2012, and saw  an overall total of 2,170 cases of dengue fever through April 2013 [no deaths] • DEN-1 was identified with probable Central or South American origin. (Alves MJ, et al. 2012) OriginVenezuela (Annelise Wilder-Smith at ASTMH Annual Meeting, Washington DC 14 Nov 2013) 2 cases importedsincefromAngola (ProMED 3 June 2013 Dengue/DHF update (46): Asia, Africa)

  19. Dengue, importedintoEurope, 2012 Madeira 2012

  20. Dengue in Europe • A large number of autochthonous cases of dengue fever (2237) occurred in Europe (Italy, France, Croatia, Madeira) during the period covered by our analysis (2007-2012) (Tomasello D, Schlagenhauf P. 2013)

  21. …any- where the mosquito vectors are found! Where dengue goes, YELLOW FEVER can follow… Beavis to Butthead

  22. But if USA & Europe, why not Asia? All of tropical Asia is infested with the yellow fever vector mosquito, Aedes aegypti

  23. Why hasn’t YF broken out in Asia? • If YF cases haveoccasionallybeenimportedintothe USA & Europe • Cases mustalsohaveoccasionallybeenimportedintoAsia • Buttherehavebeen no suchrecords in medical history

  24. Why hasn’t YF broken out in Asia? Cross-immunity theory • Asian population protected by broad cross-immunity, because of dengue, Japanese encephalitis & other flavivirus infections

  25. Why hasn’t YF broken out in Asia? BUTneitherdengue norJapaneseencephalitispatientsproduceneutralisingantibodies to YF (Makino Y et al. 1994)

  26. Why hasn’t YF broken out in Asia? • Ecuador: serologicalsurveysshowed • “...previous exposure to dengue infection may have induced an anamnestic immune response that • did not prevent yellow fever infection but • greatlyreduced the severity of the disease (Izurieta ROet al. 2009)

  27. Why hasn’t YF broken out in Asia? Vectorcompetencetheory • AsianstrainsofAedesaegyptimosquitoesnot as competentvectorsof YF as in Africa & South America? BUTtheycan still cause urbanepidemics, e.g. Nigeria 1987 (Miller BR, Monath TP, Tabachnick WJ, Ezike VI 1989)

  28. What has changed in the last 10 years? • Yellowfeverin emergingphase(Sudan & 5 more Africanoutbreaks 2012) • Dengue continues its worldwide spread • Ae. aegyptihasspread to Europe

  29. Aedesalbopictus& A. aegypti, Europe, March 2013 RUSSIA GEORGIA MADEIRA (PT) 2012 ECDC 2013

  30. What has changed in the last 10 years? • Yellowfeverin emergingphase(Sudan & 5 more Africanoutbreaks 2012) • Dengue continues its worldwide spread • Ae. aegyptispread to Europe • Airtravelconnections everfaster

  31. What has changed in the last 10 years? • Yellowfeverin emergingphase(Sudan & 5 more Africanoutbreaks 2012) • Dengue continues its worldwide spread • Ae. aegyptispread to Europe • Airtravelconnections everfaster

  32. Yellow fever, Africa 2013 Airline connections to Europe

  33. Yellow fever in capital citieswith international airports SOUTH AMERICA, 2008 Asuncion, Paraguay AFRICA, 2010 Abidjan, Côte d’Ivoire

  34. Travel times: Endemic zones  Asia (including connections) AFRICA • Abidjan (Côte d’Ivoire) Dubai Pakistan • Total 23hrs* SOUTH AMERICA • Asuncion (Paraguay)  Dubai Jakarta • Total 35hrs* *Wellwithintheincubationperiodof YF

  35. What has changed in the last 10 years? • Yellowfeverin emergingphase(Sudan & 5 more Africanoutbreaks 2012) • Dengue continues its worldwide spread • Ae. aegyptispread to Europe • Airtravelconnections everfaster • YF vaccineproductionfaltering

  36. Vaccine situation (1) • Stocks: existing world stocks (6 million doses) are insufficient to counteranepidemic in Asia • Supply: productioncannotbeexpandedfastenough to provideprotection to allofAsia(viz. currentworldwideshortageofsingle dose vials) • However, seenextpresentation in this sessionon dose-sparing solutions • Distribution: vaccinerequires a coldchain, but in some Asian countries this is probablyonlyadequate to handleenoughvaccine for SNIDs (sub-nationalimmunizationdays)

  37. Vaccine situation (2) • Application: a crash programofmass training andmobilizationofvaccinatorstakes time • Adverseeffects: 1 or 2 deathsagttributed to thevaccine(inevitableduringmasscampaigns) are sufficient to shutdown a vaccinationprogram • Resistance: some Asian countries mayresistvaccination(as hashappenedrecentlywithpoliovaccination in West Africa & measlesvaccination in Pakistan).

  38. Fake vaccination certificates (1) • Nigeria: In March 2012, 125 Nigerians on a plane to Johannesburg were denied entry and deported by the South African port health authority. The authority had concerns about the validity of the yellow fever vaccination cards • Source: ProMED • http://promedmail.org/direct.php?id=20120724.1213759

  39. Fake vaccination certificates (2) • India • In March 2011, WHO organised a consultation on the yellow fever threat to India and SE Asia in which it was concluded that the threat of introduction of YF [virus] into Asia was very real in the age of faster air travel. BUT • Black market: certificateswereissued in Indiawithoutvaccinationduringthe 2013 vaccineshortage • Source: ProMED http://www.promedmail.org/direct.php?id=20130719.1833351

  40. Fake vaccination certificates (3) • Tanzania: blackmarket in certificates • Source: ProMED • http://promedmail.org/direct.php?id=1530747 • Riskof spread by a singleapparentlyhealthyunvaccinatedpassengerincubating YF virusarriving in a country withthe mosquito vector (e.g. Chikungunyavirus: India Italy 2007)

  41. What has changed in the last 10 years? • Yellowfeverin emergingphase(Sudan & 5 more Africanoutbreaks 2012) • Dengue continues its worldwide spread • Ae. aegyptispread to Europe • Airtravelconnections everfaster • YF vaccineproductionfaltering • Fake YF vaccinationcertificates • Interruptionofmassvaccination in endemic zones

  42. Vaccine situation Interruptionofmassvaccination in manyendemic countries/areas e.g. • Francophone West & Central Africa: no massvaccinationsinceindependence -- except in areaswithoutbreaks • Nigeria: no massvaccinationsince 1987 urbanepidemics -- except in areaswithoutbreaks

  43. What has changed in the last 10 years? • Yellowfeverin emergingphase(Sudan & 5 more Africanoutbreaks 2012) • Dengue continues its worldwide spread • Ae. aegyptispread to Europe • Airtravelconnections everfaster • YF vaccineproductionfaltering • Fake YF vaccinationcertificates • Interruptionofmassvaccination in endemic zones • Failureofvectorcontrol

  44. Vector control situation Existingvectorcontrolprograms in Africa & Asia are failing to control dengue • Reintroductionof DDT could help (India) • BUTa crash programof training & deploymentof spray workerswilltake time • ANDgroundoraerialspraying: • householdersfind spray obnoxious • close uptheirhouseswhen it passes • protectingthemosquitoesinside!

  45. Hospital situation No specifictherapy for YF • Stocks of antiviral drugswillsoonbeexhausted In rural areas: • Stocks ofintravenousfluidswillsoonbeexhausted, • followedbydelay in re-supply Fortunately, YF is nottransmittedbyfomites, because • Stocks ofdisposablesyringes/needles, willrun out – & bere-usedwithassociatedrisks

  46. Diagnosis & Surveillance situation • Nobody in Asia is expecting to see a case of YF • therefore a case ofhighfeverwithjaundiceandhemorrhagicsymptomswillbeputdown to DHF, hepatitisorsomethingelse, butNOT YF • no labtest for YF willberequested • Probablyonlythenationalreferencelabwillhavereagents • preferablytherapid PCR test for YF • YF is probablynot a reportabledisease • although it shouldbe, evenunderthenew IHR

  47. Containment situation • Populacemayflee • whenplaguebroke out in Surat, India in 1994, 400 000 people(one-fifthofpopulation) fledthe city (includingdoctors & nurses!) • Some reachedNewDelhi& evenPakistan • potentiallyspreadingtheinfection

  48. Population at risk for YF, Asia 2010 Ϯsouthernprovincesunder 10° isotherm *non-UN sources 2010 UNDP Population estimates 2010

  49. Conclusion Whyhasn’t YF broken out in Asiayet? • Wedon´tknow -- BUTbecauseof • Fastairlineroutes • and YF currentlybeing in anexpansionphase • therisk is higherthan it haseverbeen, SO • if it does break out, therewillbe • insufficientvaccine, and • inadequatevectorcontrol • Withanuntreated CFR ofatleast20% -- HUGE NUMBERS OF DEATHS COULD OCCUR

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